Association of Sonic Hedgehog with the extracellular matrix requires its zinc-coordination center.

Association of Sonic Hedgehog with the extracellular matrix requires its zinc-coordination center.
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Sonic Hedgehog与细胞外基质的结合需要其锌配位中心。

DOI:
10.1186/s12860-021-00359-5
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发表时间:
2021-04-16
影响因子:
2.8
通讯作者:
Roelink H
Roelink H
中科院分区:
医学4区
文献类型:
--
作者:
Jägers C;Roelink H

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Sonic刺猬(SHH)具有锌金属肽酶的催化裂缝特征,并且与某些细菌的序列相似性与某些细菌的序列相似性,可定义M15A家族中的亚组,除了具有特征性的锌共核心外,还可以构成两个coltrane coltrane coltrane coltrane coltrane coltrane coltranix intranix intranix intranix。细菌的s肽聚糖,并参与SHH的细胞外分布。 我们发现,SHH的锌配位中心与ECM的关联以及与ECM的非单位自主信号的关联需要至少0.1μm锌,并且会通过影响持续结合的固定型固定型的催化剂的存在,从而阻止了影响关键构成的突变。 我们的结果表明,非单独的自主信号所需的SHH的假定固有肽活性是通过酶促改变ECM特性的。 在线版本包含的补充材料可获得10.1186/s12860-021-00359-5。
Sonic Hedgehog (Shh) has a catalytic cleft characteristic for zinc metallopeptidases and has significant sequence similarities with some bacterial peptidoglycan metallopeptidases defining a subgroup within the M15A family that, besides having the characteristic zinc coordination motif, can bind two calcium ions. Extracellular matrix (ECM) components in animals include heparan-sulfate proteoglycans, which are analogs of bacterial peptidoglycan and are involved in the extracellular distribution of Shh. We found that the zinc-coordination center of Shh is required for its association to the ECM as well as for non-cell autonomous signaling. Association with the ECM requires the presence of at least 0.1 μM zinc and is prevented by mutations affecting critical conserved catalytical residues. Consistent with the presence of a conserved calcium binding domain, we find that extracellular calcium inhibits ECM association of Shh. Our results indicate that the putative intrinsic peptidase activity of Shh is required for non-cell autonomous signaling, possibly by enzymatically altering ECM characteristics. The online version contains supplementary material available at 10.1186/s12860-021-00359-5.
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